PROJECT SUMMARY: Population Data & Modeling Core (PDMC) At this time, overdose deaths reduce US life expectancy and we are spending more than $500 billion per year on treating substance use disorders and their medical consequences. Considering the wide spectrum of clinical and economic consequences of substance use, the U. faces a ?syndemic? of substance use disorder, HIV, HCV, and bacterial infections. In response, we propose to replace the former HCV & HIV Core with a Population Data & Modeling Core (PDMC) that has a broader mission to use secondary data and modeling to address population outcomes of this syndemic. One powerful approach to measuring economic value is using ?big data? from the real world. Linked administrative records and data repositories from electronic health records compliment traditional prospective study designs and are an essential tool for health economics research. Administrative and clinical records are still more powerful when coupled to simulation models. Simulation models can integrate the most up-to-date knowledge about the epidemiology and natural history of substance use disorders, treatment outcomes, and resource utilization to make policy-relevant insights about treatment and care. The overall aim of CHERISH (Center for Health Economics of Treatment Interventions for Substance Use Disorder, HCV, and HIV) is to develop and disseminate economic evidence that informs substance use disorder policy and HCV and HIV care of people who use substances. In this renewal period we will expand our focus to outcome and implementation research that is conducted at the individual, system, and community levels with the following specific aims: 1) to promote the use of population data from linked administrative and clinical records in conducting community-level economic evaluations of treatment and care for substance use disorder, and HCV and HIV among people who use substances, and 2) to advance the application of simulation modeling methods to evaluations of the economic and population outcomes of substance use disorder, HCV, and HIV treatment for people who use substances. We will also leverage our unique expertise working with linked state-level administrative data across multiple state agencies in Massachusetts to help establish best practices for building and using similar databases in other states. We will collaborate with colleagues to create and sustain a network of researchers who employ simulation models to inform the response to the opioid crisis. We will sponsor an annual working group meeting, publish manuscripts identifying best practices for simulating substance use disorder and the transmission of HCV and HIV among people who inject drugs, and work closely with the Dissemination & Policy Core to develop best practices for translating simulation model outcomes into actionable policy messages.